Castration-Resistant Prostate Cancer Castration-resistant prostate cancer (CRPC) directly contributes to patient mortality. It is imperative to develop new and effective adjunct therapy to enhance the response of CRPC to hormonal therapy. Recently we developed ProFineTM, a proprietary formula consisting of bioactive flavonoids enriched in pomegranate fruit, and demonstrated its potent anti-cancer activity in CRPC cells. In this Phase I STTR application, we hypothesize that ProFineTM potently co-targets AR and Akt signaling, thereby activating apoptosis in CRPC cells and sensitizing them to androgen deprivation therapy (ADT). Two Aims are proposed: Aim 1 will determine the mechanism of action of ProFineTM in CRPC cells, specifically how ProFineTM inhibits androgen receptor signaling; Aim 2 will evaluate the efficacy of ProFineTM in enhancing enzalutamide hormonal therapy in an orthotopic model of CRPC. Accomplishment of the proposed studies will provide solid evidence for future patent application and a Phase II STTR application.